Transposable elements represent an important cause of spontaneous mutations in every organism that has been carefully examined. It is clear that genetic and environmental factors modulate the frequency of excision, insertion and rearrangement of these elements. This application proposes to study and manipulate a family of mobile elements called hobo in the fruit fly, Drosophila melanogaster. These elements have molecular and genetic properties which suggest many parallels with the P element family found in the same species. Hobo elements can be mobilized in certain genetic backgrounds. The hypothesis that these backgrounds share the presence of full length hobo elements which contribute a trans-acting transposase activity to mobilize defective hobo elements in the genome will be tested by germ- line transformation experiments. Other cis and trans factors controlling the mobilization of hobo elements will be characterized. Genetic properties associated with hobo element mobilization, such as suggestions of hybrid dysgenesis in the progeny of certain outcrosses, will be investigated. These studies are aimed at elucidating the mechanisms governing mobilization of this family of transposable elements, at understanding the relationship of the hobo elements to other dispersed mobile elements in Drosophila, and to develop techniques for exploiting hobo as a mutagen for generating transposon insertions into genes of interest, and as a vector system for hobo-mediated germ-line transformation. Ultimately, these studies will aid in understanding the regulation and effects of mobile element transpositions. Because such mobile elements are natural mutagenic and oncogenic agents which are resident in the human genome, the understanding of the biology of such elements has important medical implications. In addition, if a hobo-mediated transformation system can be developed, it might be able to operate in heterologous systems, providing a possible vector system for transformation in mammals as well as flies.